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23 November 2023: Articles  China (mainland)

A 47-Year-Old Man with Hyperphosphatemia Due to Chronic Renal Failure Treated with Lanthanum Carbonate Tablets Presenting Acutely with Partial Large Bowel Obstruction

Challenging differential diagnosis, Adverse events of drug therapy, Educational Purpose (only if useful for a systematic review or synthesis)

Qin Zhou1ABE, Mengchen Yu2ABCDEF, Xin Chang ORCID logo1AEFG, Shenglan Shang ORCID logo2CDEF, Min Li1AG*, Weitian Xu1AEG

DOI: 10.12659/AJCR.942113

Am J Case Rep 2023; 24:e942113

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Abstract

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BACKGROUND: Hyperphosphatemia is a complication of chronic renal failure (CRF) due to reduction in the glomerular filtration rate. Lanthanum carbonate is a commonly used phosphate binder for patients with CRF and hyperphosphatemia, but has adverse effects if patients are not monitored. This report is of a 47-year-old man with hyperphosphatemia due to CRF treated with lanthanum carbonate tablets who presented acutely with partial large bowel obstruction. The incidence of lanthanum carbonate causing intestinal obstruction is rare, and few cases in the literature have described the course of the disease in detail.

CASE REPORT: A 47-year-old man diagnosed with diabetic nephropathy underwent hemodialysis treatment and was prescribed 0.5 g/day of chewable lanthanum carbonate tablets. After taking lanthanum carbonate for 5 months, the patient experienced symptoms of decreased bowel movements and exhaustion, which progressively worsened. Abdominal computed tomography (CT) revealed multiple hyperdensities in the large bowel, indicating the presence of lanthanum deposition. Lanthanum carbonate was promptly discontinued. After undergoing enema and catharsis treatment, the large bowel obstruction was relieved, and the hyperdensities in the abdominal CT disappeared. The colonoscopy and histologic examination revealed ulcerations and inflammatory changes in the large bowel mucosa.

CONCLUSIONS: This report highlights the rare association between the use of lanthanum carbonate tablets and intestinal obstruction. Healthcare providers should enhance their vigilance regarding lanthanum carbonate-induced serious gastrointestinal adverse reactions and actively seek to detect lanthanum deposition by abdominal CT or radiography (X-ray). After the occurrence of lanthanum deposition, drug withdrawal and promotion of defecation are primary treatment methods.

Keywords: Drug-Related Side Effects and Adverse Reactions, Intestinal Obstruction, Lanthanum Carbonate

Background

In patients with chronic kidney disease (CKD), the ability of the kidneys to excrete phosphorus is significantly reduced, often resulting in hyperphosphatemia [1]. Treatment of hyperphosphatemia in patients with CKD mainly includes dietary control, renal replacement therapies, and the use of phosphate binders [2]. Lanthanum carbonate, a new-generation phosphate binder, is primarily indicated for the management of hyperphosphatemia. Hyperphosphatemia is a complication of chronic renal failure (CRF) that is seen in patients who undergo hemodialysis or continuous ambulatory peritoneal dialysis [3]. Lanthanum carbonate preparations mainly include chewable tablets and granules, and are predominantly formulated as chewable tablets [4]. The pharmacological mechanism involves the dissociation of the lanthanum ions from the carbonate ions when exposed to gastric acid, which then bind to phosphate in food to form insoluble lanthanum phosphate. This reduces the absorption of phosphate in the gastrointestinal tract [5]. In this process, lanthanum may be deposited in the stomach and all segments of the intestine, causing a variety of gastrointestinal adverse reactions [6,7]. Therefore, the administration of lanthanum carbonate is contraindicated in patients with intestinal obstruction, intestinal impaction, or fecal impaction [5]. Mild to moderate gastrointestinal adverse effects, including abdominal pain, nausea, constipation, and vomiting are common in patients taking lanthanum carbonate [5]. Serious adverse drug reactions such as gastrointestinal ulceration, intestinal bleeding, stool incarceration, and intestinal obstruction are rare occurrences [5]. The incidence of intestinal obstruction is less than 1% [5], and few reports in the literature have comprehensively described the diagnosis and treatment process. Colonoscopy and large bowel mucosal pathology results are seldom reported [8].

This report is of a 47-year-old man with hyperphosphatemia due to CRF treated with lanthanum carbonate tablets who presented acutely with partial large bowel obstruction. We identified some analogous case reports wherein patients developed substantial accumulation of lanthanum deposits within the large bowel [9–11]. The highlight of this article is the detailed description of the diagnosis and treatment process, the comprehensive presentation of abdominal computed tomography (CT), colonoscopy, and pathological findings, as well as discussion of the clinical manifestations and treatment focus of lanthanum carbonate-induced large bowel obstruction.

Case Report

In December 2021, a 47-year-old man was diagnosed with diabetic nephropathy, uremia, hyperphosphatemia, and hypertension. The patient was placed on hemodialysis and prescribed 0.5 g/d of chewable lanthanum carbonate tablets. Other concurrent medications included calcitriol soft capsules, clopidogrel hydrogen sulfate tablets, coenzyme Q10 tablets, atorvastatin calcium tablets, nifedipine sustained-release tablets, insulin aspart injection, and insulin degludec injection. In May 2022, the patient exhibited gastrointestinal symptoms including reduced gas and dejection, which were able to be partially alleviated with the medication lactulose. In June 2022, these symptoms worsened: the patient presented with postprandial vomiting that contained stomach contents, without abdominal pain. The patient had no prior history of digestive system disorders. The patient’s diet remained unchanged throughout the course of the disease.

The patient was hospitalized in June 2022. Abdominal CT detected multiple hyperdensities in the large bowel, slight thickening of the transverse intestinal wall, and narrowing of the lumen (Figure 1A, 1B). Laboratory tests showed leukocytes present in the stool (3–5 visible on high power magnification). Routine blood tests indicated normal white blood cell count, serum phosphate and calcium levels, but decreased red blood cell counts and platelet counts. Abdominal examination upon admission revealed hypogastric palpable masses without other positive signs in the abdomen.

According to the above examination results, the diagnosis was partial large bowel obstruction caused by lanthanum carbonate. It was suggested to discontinue the use of lanthanum carbonate chewable tablets and switch to other phosphate-lowering drugs. Treatment as follows was conducted for 9 days: Each day, a high enema of either magnesium sulfate or saline was administered, along with lactulose or polyethylene glycol electrolytes and mosapride to facilitate bowel movements. During the treatment period, the patient’s bowel activity increased, stool volume increased, and there was no further vomiting. After 9 days of treatment, the patient underwent colonoscopy and another abdominal CT. The colonoscopy showed a large ulceration on the mucous membrane of the large bowel, covered with a thin layer of white moss (Figure 2). Biopsy findings included ulcerations, some inflammatory necrosis, and granulation tissue (Figure 3). After treatment, abdominal CT revealed that the hyperdensities in the large bowel had almost disappeared (Figure 1C, 1D).

Over a followup period of 6 months, the patient had normal bowel movements and did not experience any gastrointestinal discomfort. He did not restart on lanthanum carbonate chewable tablets.

Discussion

Healthcare providers should be alert to intestinal obstruction due to lanthanum deposition, especially in patients who have been taking lanthanum carbonate for a long time or chewing insufficiently. As mentioned in the Background section, gastrointestinal adverse reactions in patients taking lanthanum carbonate may present with a broad spectrum of clinical features, posing a challenge to accurate diagnosis [5–7]. Prolonged drug therapy and insufficient chewing escalate the risk of drug deposition [11]. In our case, the patient experienced difficulty defecating after 5 months of lanthanum carbonate administration, which is consistent with the time of onset in the literatures [9,10,12]. Fortunately, this case was diagnosed early and did not develop to intestinal perforation or abdominal infection [9,11].

The differential diagnosis of adverse drug reactions was performed by elimination. Abdominal CT and radiography (X-ray) are convenient and valid diagnostic methods when lanthanum deposition is suspected [12]. X-rays are unable to penetrate lanthanum [13]. In the literature on lanthanum carbonate-induced gastrointestinal adverse reactions, a “star-like” appearance or opacities are often observed on abdominal CT and X-ray [9–12,14]. Even non-transparent crushed lanthanum carbonate tablets have been found in the gastrointestinal tract [15]. In our case, according to the Naranjo Adverse Drug Reaction Probability Scale [16], the association between the use of lanthanum carbonate and the patient’s symptoms of partial large bowel obstruction was deemed to be highly probable. After treatment, abdominal CT showed that the high-density shadow disappeared, no tumor lesions were found in the abdomen, and the condition did not rebound after discharge. Therefore, malignant tumor as the cause of large bowel obstruction could be excluded. The patient showed normal white blood cells count, no fever, and no abdominal pain, which could rule out large bowel obstruction caused by intestinal infection. Judging from imaging examinations, past medical history, and the patient’s condition after discharge, there was no evidence suggesting that the patient had abdominal hernia, intestinal adhesion, or any other general causes of large bowel obstruction. Except for lanthanum carbonate chewable tablets, other medications for chronic diseases continued to be taken, ruling out the possibility that the large bowel obstruction was caused by another drug. The differential diagnosis in this and other cases relied heavily on abdominal imaging as a crucial step. A definitive diagnosis can be established by identifying typical abdominal imaging findings indicative of lanthanum deposition, while ruling out other potential causes.

The imaging and histological features of gastroduodenal lanthanum deposition have been summarized in a few manuscripts [17]. However, there are relatively few reports about large bowel lanthanum deposition [9–11]. In the present paper, we reported colonoscopy and pathological findings of lanthanum deposition in the large bowel. We observed ulceration visible by colonoscopy, inflammatory necrosis, and granulation tissue in the pathological examination, which was consistent with the intestinal histopathological findings in the previously reported cases [8,17]. These results indicate that the adverse reactions in the gastrointestinal tract caused by lanthanum deposition are closely related to damage of the mucosal barrier.

In our opinion, the primary principle in managing adverse effects caused by lanthanum carbonate is to discontinue the medication and switch to other phosphate-lowering drugs. Additionally, the use of enemas and cathartics should be considered if necessary. Most of the existing literature on the gastrointestinal adverse effects induced by lanthanum carbonate only mentioned discontinuing the use of lanthanum carbonate, without considering enema, catharsis, and gastrointestinal motility therapy [12]. In one case of lanthanum carbonate that caused perforation of the colonic diverticulum, there were still large lanthanum deposits in the intestine 9 days after discontinuation of the lanthanum carbonate [9]. In another case of constipation caused by lanthanum carbonate, which was similar to our case, enema and laxatives were given, and clinical symptoms were completely relieved after treatment [10]. Therefore, we believe that serious gastrointestinal adverse effects caused by lanthanum carbonate, such as intestinal obstruction, require more aggressive treatment, including enema and laxative therapy.

Conclusions

When patients taking lanthanum carbonate experience gastrointestinal discomfort, healthcare providers should thoroughly consider the possibility of adverse drug reactions. The most effective diagnostic tests include abdominal CT or X-ray, which may present as a characteristic “star-like” appearance or opacities. Following the occurrence of lanthanum deposition, primary treatments involve discontinuation of lanthanum carbonate and promotion of defecation.

References:

1.. Hruska KA, Mathew S, Lund R, Hyperphosphatemia of chronic kidney disease: Kidney Int, 2008; 74(2); 148-57

2.. Barreto FC, Barreto DV, Massy ZA, Drake TB, Strategies for phosphate control in patients with CKD: Kidney Int Rep, 2019; 4(8); 1043-56

3.. Floege J, Phosphate binders in chronic kidney disease: An updated narrative review of recent data: J Nephrol, 2020; 33; 497-508

4.. , Lanthanum carbonate Available from: https://www.drugfuture.com/fda/drugsearch.aspx

5.. , FOSRENOL (lanthanum carbonate) Chewable Tablets Approval, 2004. Prescribing Information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021468s018lbl.pdf

6.. Cernaro V, Calimeri S, Laudani A, Santoro D, Clinical evaluation of the safety, efficacy and tolerability of lanthanum carbonate in the management of hyperphosphatemia in patients with end-stage renal disease: Ther Clin Risk Manag, 2020; 16; 871-80

7.. Hutchison AJ, Wilson RJ, Garafola S, Copley JB, Lanthanum carbonate: Safety data after 10 years: Nephrology (Carlton), 2016; 21(12); 987-94

8.. Goto K, Ogawa K, Lanthanum deposition is frequently observed in the gastric mucosa of dialysis patients with lanthanum carbonate therapy: a clinicopathologic study of 13 cases, including 1 case of lanthanum granuloma in the colon and 2 nongranulomatous gastric cases: Int J Surg Pathol, 2016; 24(1); 89-92

9.. Korzets A, Tsitman I, Lev N, Lanthanum, constipation, baffling X-rays and a perforated colonic diverticulum: Clin Kidney J, 2012; 5(4); 331-33

10.. Camarero-Temiño V, Mercado-Valdivia V, Hijazi-Prieto B, Abaigar-Luquin P, Intestinal pseudo-obstruction secondary to persistent constipation due to lanthanum carbonate: Nefrologia, 2012; 32(1); 129

11.. Kurita N, Uchihara H, Fecalith formation and colonic perforation after lanthanum carbonate granules administration: Am J Kidney Dis, 2014; 63(5); 861-62

12.. Kampmann J, Hansen NP, Ørsted Schultz AN, Lanthanum carbonate opacities – a systematic review: Diagnostics (Basel), 2022; 12(2); 464

13.. Iwamuro M, Urata H, Tanaka T, Okada H, Review of the diagnosis of gastrointestinal lantha-num deposition: World J Gastroenterol, 2020; 26(13); 1439-49

14.. Chang FM, Tarng DC, Yang CY, Starry-sky bowels: Int J Colorectal Dis, 2018; 33(12); 1807-8

15.. Singanamala S, Roer DA, Perazella MA, An unexpected finding on chest roentgenogram following hemodialysis catheter placement: Semin Dial, 2008; 21(3); 293-94

16.. Naranjo CA, Busto U, Sellers EM, A method for estimating the probability of adverse drug reactions: Clin Pharmacol Ther, 1981; 30(2); 239-45

17.. Davis RL, Abraham JL, Lanthanum deposition in a dialysis patient: Nephrol Dial Transplant, 2009; 24(10); 3247-50

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923